Serum Cholesterol Esters Research Articles

Lipid Profile and Fatty-Acid Composition of Human Serum in Hypertension Patients

The aim of this study was designed to determine the effect of hypertension on the level of lipid fractions and percentage of fatty acids in serum . The study included( 50) patients with hypertension ,blood was taken after( 10-12) hour fasting . The age of patients was between (60-80) year. Blood samples from (50) normal subject with the same age were collected as control .The patients samples collection were from the medical word . A number of biochemical parameters were measured using enzymatic kits methods also the analysis and the measurement of percentage of fatty acids in fatty component of serum (cholesterol ester, phospholipids ,triglyceride) separated by thin layer chromatography(TLC) followed by transmethylation of fatty acids and measurement of fatty acids percentage using Capillary Gas Chromatography (CGC).The result of this study showed that there is a significant differences in the level of studied biochemical parameter and fatty acids percentage in hypertension patients compared with the control group. The results of this study also showed that a significant increase in level of (TG) in serum of hypertension patients . The result showed that a significant increase in percentage of (PUFA) in (PL) part

Cross-sectional relationships between dietary fat intake and serum cholesterol fatty acids in a Swedish cohort of 60-year-old men and women.

The present study aimed to describe the relationship between self-reported dietary intake and serum cholesterol fatty acids (FAs) in a Swedish population of 60-year-old men and women. Cross-sectional data collected in 1997-1998 from 4232 individuals residing in Stockholm County were used. Five diet scores were created to reflect the intake of saturated fats in general, as well as fats from dairy, fish, processed meat and vegetable oils and margarines. Gas chromatography was used to assess 13 FAs in serum cholesterol esters. The association between each diet score and specific FAs was assessed by percentile differences (PD) with 95% confidence intervals (CI) at the 10th, 25th, 50th, 75th and 90th percentile of each FA across levels of diet scores using quantile regression. Fish intake was associated with high proportions of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). For each point increase in fish score, the 50th PD in EPA and DHA was 32.78% (95% CI = 29.22% to 36.35%) and 10.63% (95% CI = 9.52% to 11.74%), respectively. Vegetable fat intake was associated with a high proportion of linoleic acid and total polyunsaturated fatty acids (PUFA) and a low proportion of total saturated fatty acids (SFA). The intake of saturated fats in general and dairy fat was slightly associated with specific SFA, although the intake of fat from meat was not. In the present study population, using a rather simple dietary assessment method, the intake of fish and vegetable fats was clearly associated with serum PUFA, whereas foods rich in saturated fats in general showed a weak relationship with serum SFA. Our results may contribute to increased knowledge about underlying biology in diet-cardiovascular disease associations.

Polyunsaturated Fat Intake Estimated by Circulating Biomarkers and Risk of Cardiovascular Disease and All-Cause Mortality in a Population-Based Cohort of 60-Year-Old Men and Women.

High intake of polyunsaturated fatty acids (PUFAs) may reduce the risk of cardiovascular disease (CVD) and mortality. Large, prospective studies including both sexes and circulating PUFAs as dietary biomarkers are needed. We investigated sex-specific associations of the major dietary PUFAs, eicosapentaenoic acid, docohexaenoic acid, linoleic acid, and α-linolenic acid, with incident CVD and all-cause mortality in a population-based cohort. PUFAs in serum cholesterol esters were measured at baseline in 60-year-old Swedish women (n=2193) and men (n=2039). With the use of national registers, 484 incident CVD events (294 men and 190 women) and 456 all-cause deaths (265 men and 191 women) were identified during follow-up (median, 14.5 years) in individuals without prior CVD at baseline. Associations of PUFAs with CVD and mortality were evaluated with Cox proportional hazard models. In multivariable-adjusted models, 1-SD increases in eicosapentaenoic acid and docohexaenoic acid were associated with lower risk of incident CVD among women (hazard ratio [HR], 0.79 [95% confidence interval (CI), 0.64-0.97] and 0.74 [95% CI, 0.61-0.89], respectively). α-Linolenic acid was associated with moderately increased CVD risk in women (HR, 1.16; 95% CI, 1.02-1.32). Inverse associations with all-cause mortality were observed for eicosapentaenoic acid and docohexaenoic acid among all participants (HR, 0.81 [95% CI, 0.72-0.91] and 0.80 [95% CI, 0.72-0.89], respectively) and for linoleic acid in men (HR, 0.73; 95% CI, 0.64-0.83). Serum linoleic acid and very-long-chain n-3 PUFAs, partly reflecting vegetable oil and fish intake, respectively, were inversely associated with all-cause mortality. Inverse associations of eicosapentaenoic acid and docohexaenoic acid with incident CVD were observed only in women.

Association of lecithin-cholesterol acyltransferase activity measured as a serum cholesterol esterification rate and low-density lipoprotein heterogeneity with cardiovascular risk: a cross-sectional study.

The cholesterol-esterifying enzyme, lecithin-cholesterol acyltransferase (LCAT), is believed to play a key role in reverse cholesterol transport. However, recent investigations have demonstrated that higher LCAT activity levels increase the formation of triglyceride (TG)-rich lipoproteins (TRLs) and atherogenesis. We hypothesized that higher LCAT activity measured as a serum cholesterol esterification rate by the endogenous substrate method might increase the formation of TRLs and thereby alter low-density lipoprotein (LDL) heterogeneity. The estimated LDL particle size [relative LDL migration (LDL-Rm)] was measured by polyacrylamide gel electrophoresis with the LipoPhor system (Joko, Tokyo, Japan) in 538 consecutive patients with at least risk factor for atherosclerosis. Multivariate regression analysis after adjustments for traditional risk factors identified elevated TRL-related marker (TG, remnant-like particle cholesterol, apolipoprotein C-II, and apolipoprotein C-III) levels as independent predictors of smaller-sized LDL particle size, both in the overall subject population and in the subset of patients with serum LDL cholesterol levels of <100mg/dL. Area under the receiver operating characteristic curve of the LCAT activity (0.79; sensitivity 60%; specificity 84.8%) was observed for the evaluation of the indicators of an LDL-Rm value of ≥0.40, which suggests the presence of large amounts of small-dense LDL. The results lend support to the hypothesis that increased LCAT activity may be associated with increased formation of TRLs, leading to a reduction in LDL particle size. Therefore, to reduce the risk of atherosclerotic cardiovascular disease, it may be of importance to pay attention not only to a quantitative change in the serum LDL-C, but also to the LCAT activity which is possibly associated with LDL heterogeneity.

Genome‐Wide Association Studies (GWAS) of Estimated Fatty Acid Desaturase Activity in Serum and Adipose Tissue: Relationships with Insulin Sensitivity

Fatty acid desaturases (FADS) catalyze formation of mono‐ and polyunsaturated fatty acids (FA) and have been related to insulin sensitivity (IS). FADS activities differ between tissues and are influenced by genetic factors that may affect the link to IS.The study aimed at identifying genetic variants influencing estimated FADS activity in serum cholesterol esters (CE) and adipose tissue (AT); and to evaluate if identified loci affect IS.GWAS of Δ9‐ (D9D), Δ6‐ (D6D), and Δ5‐desaturase (D5D) activities (estimated by product‐to‐precursor FA ratios analyzed by gas chromatography) in CE (n=1,453, 70% men) and AT (n=783, all men) were performed in two Swedish population‐based cohorts. Associated loci (P &lt;5.0E‐8) were evaluated for associations with IS measured by hyperinsulinemic euglycemic clamp (n=554).Variants in one locus (FADS1) were strongly associated with D5D in CE (P=1.9E‐70) and AT (P=1.1E‐27). Variants in three loci were associated at a genome wide‐significant level with CE D6D (FADS2, P=3.0E‐67; PDXDCI, P= 4.8E‐8; and near MC4R, P=3.7E‐8) and one with AT D9D (PKDL1, P=2.2E‐19). After Bonferroni correction, one locus was significantly associated with IS (PDXDCI, P=0.030).FADS genes determined estimated FADS activity, although FA ratios in AT and CE represent FADS activities in separate tissues and are thus influenced by different genetic factors with potential effects on IS.The Wellcome Trust funded the study.

A low carbohydrate, high protein diet suppresses intratumoral androgen synthesis and slows castration-resistant prostate tumor growth in mice

Dietary factors continue to preside as dominant influences in prostate cancer prevalence and progression-free survival following primary treatment. We investigated the influence of a low carbohydrate diet, compared to a typical Western diet, on prostate cancer (PCa) tumor growth in vivo. LNCaP xenograft tumor growth was studied in both intact and castrated mice, representing a more advanced castration resistant PCa (CRPC). No differences in LNCaP tumor progression (total tumor volume) with diet was observed for intact mice (P=0.471) however, castrated mice on the Low Carb diet saw a statistically significant reduction in tumor growth rate compared with Western diet fed mice (P=0.017). No correlation with serum PSA was observed. Steroid profiles, alongside serum cholesterol and cholesteryl ester levels, were significantly altered by both diet and castration. Specifically, DHT concentration with the Low Carb diet was 58% that of the CRPC-bearing mice on the Western diet. Enzymes in the steroidogenesis pathway were directly impacted and tumors isolated from intact mice on the Low Carb diet had higher AKR1C3 protein levels and lower HSD17B2 protein levels than intact mice on the Western diet (ARK1C3: P=0.074; HSD17B2: P=0.091, with α=0.1). In contrast, CRPC tumors from mice on Low Carb diets had higher concentrations of both HSD17B2 (P=0.016) and SRD5A1 (P=0.058 with α=0.1) enzymes. There was no correlation between tumor growth in castrated mice for Low Carb diet versus Western diet and (a) serum insulin (b) GH serum levels (c) insulin receptor (IR) or (d) IGF-1R in tumor tissue. Intact mice fed Western diet had higher serum insulin which was associated with significantly higher blood glucose and tumor tissue IR. We conclude that both diet and castration have a significant impact on the endocrinology of mice bearing LNCaP xenograft tumors. The observed effects of diet on cholesterol and steroid regulation impact tumor tissue DHT specifically and are likely to be mechanistic drivers behind the observed tumor growth suppression.

Effects of Aster scaber Seed Oil Containing trans-Δ3 Fatty Acids on Lipid Profiles of Hamsters and Rats.

The effects of Aster scaber seed oil (ASO) on lipid profiles were studied in rats and hamsters. ASO contained considerable amounts of Δ3t-16:1 (11.4%), Δ3t, 9c-18:2 (4.6%), and Δ3t, 9c, 12c-18:3 (11.3%). Young rats and hamsters were fed diets containing ASO, soybean oil (SBO), or olive oil (OLO) as fat sources for 4 weeks in separate experiments with or without cholesterol. In the rat study, there were no significant differences in the concentrations of serum total cholesterol, high-density lipoprotein (HDL)-cholesterol, and triacylglycerol among the groups. The serum but not liver malondialdehyde (MDA) level was significantly lower in the ASO-fed group than it was in the other groups. The biochemical and growth parameters revealed no significant biological damages in the ASO-fed animals. In the hamster study, dietary cholesterol-dependent effects were evident in the serum lipids profiles, whereas the fat-induced effect was only observed in the ratio of serum low-density lipoprotein (LDL)-/HDL-cholesterol. Furthermore, fat- and cholesterol-induced effects were evident in the ratio of serum LDL-/HDL-cholesterol. Significant interactions between dietary fat and cholesterol were observed as evident from the concentration of serum cholesterol and triacylglycerol, as well as the activity of serum cholesterol ester transfer protein. These results suggest that dietary ASO containing trans-Δ3 fatty acids appeared to improve the serum LDL-/HDL-cholesterol ratio more than the SBO did, especially when hamsters were simultaneously fed cholesterol-supplemented diet.

Cholesterol and lipoprotein metabolism: Early Career Committee contribution.

Cholesterol and lipoprotein metabolism: Early Career Committee contribution.

Unavailability of liver triacylglycerol increases serum cholesterol concentration induced by dietary cholesterol in exogenously hypercholesterolemic (ExHC) rats.

BackgroundExogenously hypercholesterolemic (ExHC) rats develop hypercholesterolemia and low hepatic triacylglycerol (TAG) levels when dietary cholesterol is loaded. The responsible gene Smek2 was identified via linkage analysis using the original strain Sprague–Dawley (SD) rats. In this study, we compared SD and ExHC rats to investigate a relationship between hypercholesterolemia and the low hepatic TAG levels observed in ExHC rats.MethodsMale 4-weeks-old ExHC and SD rats were fed a 1% cholesterol diet for 1 week. Serum and liver parameters were analyzed. Gene expression and enzyme activities related to TAG metabolism were also assessed.ResultsWe reproducibly observed higher serum cholesterol and lower hepatic TAG levels in ExHC rats than in SD rats. Golgi apparatus in the livers of ExHC rats secreted β-very-low-density lipoprotein (β-VLDL) that had higher cholesterol ester (CE) and lower TAG content than those in the β-VLDL secreted by SD rats. Gene expression related to fatty acid and TAG synthesis in ExHC rats was lower than that in SD rats. Enzymatic activities for fatty acid synthesis were also relatively lower in ExHC rats. Moreover, the fatty acid composition of hepatic and serum CE in ExHC rats showed that these CEs were not modified after secretion from the liver despite the similar activities of serum lecithin-cholesterol acyltransferase (LCAT) in ExHC rats to those in SD rats.ConclusionsLow production of liver TAG and secretion of CE-rich, TAG-poor β-VLDL without modification by LCAT in the circulation contributed to hypercholesterolemia induced by dietary cholesterol in ExHC rats.

Influence of a healthy Nordic diet on serum fatty acid composition and associations with blood lipoproteins – results from the NORDIET study

BackgroundThe fatty acid (FA) composition of serum lipids is related to the quality of dietary fat intake.ObjectiveTo investigate the effects of a healthy Nordic diet (ND) on the FA composition of serum cholesterol esters (CE-FA) and assess the associations between changes in the serum CE-FA composition and blood lipoproteins during a controlled dietary intervention.DesignThe NORDIET trial was a 6-week randomised, controlled, parallel-group dietary intervention study that included 86 adults (53±8 years) with elevated low-density lipoprotein cholesterol (LDL-C). Serum CE-FA composition was measured using gas chromatography. Diet history interviews were conducted, and daily intake was assessed using checklists.ResultsFood and nutrient intake data indicated that there was a reduction in the intake of fat from dairy and meat products and an increase in the consumption of fatty fish with the ND. The levels of saturated fatty acids in cholesterol esters (CE-SFA) 14:0, 15:0, and 18:0, but not 16:0, showed a significant decrease after intake of ND compared to the control diet (p<0.01). Also, a significant increase in serum 22:6n – 3 was observed compared with the control diet (p<0.01). The changes in CE-SFA 14:0, 15:0, and 18:0 correlated positively with changes in LDL-C, HDL-C, LDL-C/HDL-C, ApoA1, and ApoB (p<0.01), respectively, whereas the changes in polyunsaturated fatty acids in cholesterol esters (CE-PUFA) 22:6n – 3 were negatively correlated with changes in the corresponding serum lipids.ConclusionsThe decreased intake of saturated fat and increased intake of n-3 PUFA in a healthy ND is partly reflected by changes in the serum CE-FA composition, which are associated with an improved serum lipoprotein pattern.

Saturated fatty acid (SFA) status and SFA intake exhibit different relations with serum total cholesterol and lipoprotein cholesterol: a mechanistic explanation centered around lifestyle-induced low-grade inflammation

We investigated the relations between fatty acid status and serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol and total cholesterol/HDL cholesterol ratio in five Tanzanian ethnic groups and one Dutch group. Total cholesterol/HDL cholesterol ratio is a widely used coronary artery disease (CAD) risk factor. Fatty acid status was determined by measurement of fatty acids in serum cholesterol esters and erythrocytes. Data reflecting the influence of fatty acid intakes on serum total cholesterol and lipoprotein cholesterol were obtained from documented intervention studies. We found that 14:0, 16:0 and saturated fatty acid (SFA) status correlates positively with total cholesterol/HDL cholesterol ratio, while their intakes were unrelated. Linoleic acid and polyunsaturated fatty acid (PUFA) status and PUFA intake exhibited negative relations with the total cholesterol/HDL cholesterol ratio. These data suggest that a high SFA status, not a high SFA intake, is associated with increased CAD risk, while both high linoleic acid status and PUFA status are associated with reduced CAD risk. Consequently, the total cholesterol/HDL cholesterol ratio is a questionable risk marker since meta-analyses of randomized controlled trials show that partial dietary replacement of SFA for linoleic acid, the dominating dietary PUFA, does not change CAD risk. We conclude that many lifestyle factors, not SFA intake alone, determine SFA status, and suggest that interaction with many other lifestyle factors determines whether SFA status has a relevant contributing effect in low-grade inflammation, lipoprotein changes and CAD risk. The present outcome may teach us to consider the health effects of the entire diet together with many nondietary lifestyle factors, opposite to the reductionist approach of studying the effects of single nutrients, SFA and PUFA included.

Polyunsaturated fatty acids in serum and homocysteine concentrations in Japanese men and women: a cross-sectional study

BackgroundSupplementation studies have suggested a role of n-3 polyunsaturated fatty acids (PUFAs) in homocysteine metabolism, but the evidence is limited and inconsistent among studies that measured blood levels of n-3 and n-6 PUFAs. We examined the association between blood levels of PUFAs and homocysteine in Japanese men and women.MethodsThe subjects were 496 employees (290 men and 206 women) of 2 municipal offices in Japan. Fatty acid composition in serum phospholipids and cholesterol ester (CE) was measured using gas–liquid chromatography. Multiple regression was used to calculate means of homocysteine concentrations according to PUFA tertile with adjustment for potential confounders.ResultsSerum homocysteine concentration decreased with increasing levels of total n-3 PUFA, eicosapentaenoic acid and docosahexaenoic acid (DHA) in serum phospholipids and CE with adjustment for age, sex and workplace. However, only DHA in serum phospholipids remained statistically significant after additional adjustment for other potential confounders including serum folate (P-trend = 0.04). N-6 PUFAs were not significantly associated with homocysteine concentrations.ConclusionsHigher proportion of DHA in serum phospholipids may be associated with lower homocysteine concentrations in Japanese men and women.

Cholesterol and its esters as serum biomarkers in malignant obstructive jaundice: a single step 1H NMR metabolomic approach

The paucity of biomarkers for malignant obstructive jaundice results in formidable morbidity and mortality rates. Therefore, alternative diagnostic measures are required for improved clinical interpretation and better peri-operative management of patients. In the present study, 1H NMR-based metabolomic approach has been applied to investigate serum and bile based metabolic biomarkers in benign and malignant causes of obstructive jaundice (OBJ). Serum and bile specimens from benign OBJ patients (n = 28), malignant OBJ patients (n = 36) and serum of healthy controls (n = 57) were analysed by 1H NMR spectroscopy. Quantitation of eight serum metabolites (isobutyrate, lactate, alanine, acetone, glutamine, creatine, threonine and 1-methylhistidine) was carried out. A newer and rapid single step NMR based semi-quantitative ratio analysis of serum total cholesterol (tCho), cholesterol (Chol) and cholesterol ester (CE) were performed in deuterated dimethyl sulfoxide-d6. In bile, total bile acids, cholesterol, phosphatidylcholine, glycerophosphatidylcholine and urea were quantified. The effect of benign and malignant OBJ on small metabolites and lipids were statistically analysed by Mann–Whitney U test and multivariate discriminant function analysis. It was found that malignancy could be differentiated from benign cases of OBJ with a correct classification of 85.7 % when eight serum metabolites in combination with ratios of serum cholesterol were analysed. Significant alterations in serum tCho, Chol, CE and serum metabolites may have potential for early and differential non-invasive diagnosis of malignant and benign OBJ cases. It will further augment the novel insights of local and systemic effects in OBJ patients.

Childhood Serum Fatty Acid Quality Is Associated with Adult Carotid Artery Intima Media Thickness in Women but Not in Men

AbstractChildhood nutrition may play a role in the development of cardiovascular disease risk in adulthood. We examined the links between childhood dietary fatty acid quality and adult subclinical atherosclerosis in a cohort of 374 males and 449 females, aged 3–18 y at baseline in 1980, followed for 27 y. Serum cholesterol ester fatty acid (CEFA) percentages were analyzed as markers of dietary fatty acid intake. Adulthood carotid artery intima media thickness (cIMT, μm), adjusted for childhood and adulthood lipid and nonlipid risk markers, was used as the outcome. In women, after adjustment for age and childhood nonlipid risk markers, the childhood saturated CEFA (B = 11.3; P = 0.011), monounsaturated CEFA (B = 2.5; P = 0.025), and n3 (ω3) polyunsaturated CEFA (B = 16.2; P = 0.035) percentages were directly associated with adult cIMT. In contrast, the n6 (ω6) polyunsaturated CEFA percentage was negatively associated with cIMT (B = −2.3; P = 0.008). Similar relationships were observed between childhood dietary intake data and adult cIMT. In men, these associations were generally weak and nonsignificant (P > 0.05) after controlling for confounders. These longitudinal data suggest that fat quality as reflected in the serum cholesterol ester fraction in childhood is associated with adult cIMT in women.

Abstract 111: A Novel Assay that Incorporates Measurement of Ex Vivo LCAT Activity with Measurement of Cholesterol Efflux Capacity - Assessment of Two Biomarkers of Serum HDL Function

Atheroprotective properties of high-density lipoproteins (HDL) may be due to the ability to remove lipids from peripheral cells to the liver for excretion during reverse cholesterol transport (RCT). Assays that measure functionality of serum HDL are needed to evaluate the therapeutic potential of treatments targeting HDL metabolism. Recent work shows an inverse correlation between cholesterol efflux capacity of serum HDL and coronary artery disease, demonstrating the value of measuring HDL functionality. Another function of HDL that promotes RCT is the capacity for esterification of cholesterol by lecithin:cholesterol acyltransferase (LCAT). A novel assay was developed that in addition to measurement of serum HDL efflux capacity incorporates measuring the capacity for esterification of HDL-cholesterol by LCAT. Assay methodology includes measurement of global cholesterol efflux via all known pathways (ABCA1, SR-BI, ABCG1 and passive diffusion) from J774 macrophage cells to serum HDL, and measurement of the proportion of cholesterol transferred to serum HDL that is esterified by LCAT over 4h. Assay validation included assessment of intra-assay repeatability, inter-assay precision, linearity, LOQ and specificity. Results showed the intra-assay variability (%CV) from six independent preparations of serum HDL is ≤10% for both the % efflux and the % esterification of cholesterol. Inter-assay variability between four separate assays is ≤13% for both the % efflux and the % esterification of cholesterol. Cholesterol efflux is linear up to concentrations of 2.8% serum HDL and cholesterol esterification is linear up to concentrations of 4% serum. The LOQ for the assay is 0.15% cholesterol efflux and 0.40% cholesterol esterification. Global cholesterol efflux was determined to be specific for known cholesterol acceptors such as serum HDL (p≤0.0001 versus media blank). The cholesterol esterification measured was determined to be specific for the action of LCAT because the presence of LCAT inhibitor decreased the % ester by 86-97% (p≤0.0009). This novel assay allows the measurement of two functional aspects of an individual subject’s serum HDL, the capacities for both cholesterol efflux and for esterification of cholesterol by LCAT.

An environmental wide association study (EWAS) approach to the metabolic syndrome

BackgroundEnvironmental contaminants have previously been linked to components of the Metabolic Syndrome (MetS). However, exposure to environmental contaminants is in part determined by various lifestyle factors. ObjectiveUsing an “Environmental Wide Association Study” (ELWAS) integrating environmental contaminants and lifestyle factors, we aimed to evaluate a possible additive role of both contaminants and lifestyle factors regarding MetS. Methods1016 subjects aged 70years were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. 43 environmental contaminants were measured in the circulation. Dietary records were used to evaluate 21 nutrients and the proportions of 13 fatty acids were determined in serum cholesterol esters to further quantify fat quality intake. Adding 5 other important lifestyle factors yielded together 76 environmental and lifestyle factors. MetS was defined by the NCEP/ATPIII-criteria. Results23% had MetS. Using cross-validation within the sample, fourteen environmental contaminants or lifestyle factors consistently showed a false discovery rate <0.05. When the major variables entered a multiple model, only p, p′-DDE levels (positive), PCB209 (inverse) and exercise habits (inverse) were together with a fatty acid pattern, with high levels of palmitic acid and oleic acid and low levels of linoleic acid, related to MetS (p<0.002 for all variables). ConclusionUsing a cross-sectional EWAS approach, certain environmental contaminants and lifestyle factors were found to be associated with prevalent metabolic syndrome in an additive fashion in an elderly population.

Increased Serum Cholesterol Esterification Rates Predict Coronary Heart Disease and Sudden Death in a General Population

Lecithin:cholesterol acyltransferase (LCAT) is thought to be important in reverse cholesterol transport. However, its association with coronary heart disease (CHD) and sudden death is controversial. We prospectively studied 1927 individuals from the general population. Serum concentrations of apolipoprotein A-I, A-II, B, C-II, C-III, E, and LCAT activity measured as a serum cholesterol esterification rate were evaluated. We documented 61 events of CHD and sudden death during 10.9 years of follow-up. After adjustment for age and sex, LCAT activity was significantly associated with the risk of CHD and sudden death (hazard ratio, 3.02; 95% confidence interval, 1.49-6.12; P=0.002). In multivariate analysis adjusted for age, sex, current smoking status, history of diabetes mellitus, body mass index, systolic blood pressure, serum total cholesterol, and serum high-density lipoprotein cholesterol concentrations, the hazard ratio of LCAT activity for the risk of CHD and sudden death remained significant (hazard ratio, 3.07; 95% confidence interval, 1.35-7.01; P=0.008). However, when it was analyzed for men and women separately, this association remained significant only in women. Increased LCAT activity measured as a serum cholesterol esterification rate was a risk for CHD and sudden death in a Japanese general population.

Serum and adipose tissue fatty acid composition as biomarkers of habitual dietary fat intake in elderly men with chronic kidney disease

Fatty acid (FA) composition in serum cholesterol esters (CE) and adipose tissue (AT) reflect the long-term FA intake in the general population. Because both dietary intake and FA biomarkers associate with renal function, our aim was to identify which CE and AT FAs are useful biomarkers of habitual FA intake in individuals with chronic kidney disease (CKD). Cross-sectional analysis was performed in 506 men (aged 70 years) with a glomerular filtration rate (GFR) of <60 mL/min per 1.73 m(2) from the Uppsala Longitudinal Study of Adult Men cohort. Dietary habits were evaluated with a 7-day dietary record. FA compositions in CE and AT were analyzed by gas-liquid chromatography in two random subsamples of 248 and 318 individuals, respectively. Both CE and AT linoleic acid and docosahexaenoic acid (DHA) were strongly associated with their corresponding intake, after adjustments for non-dietary factors. The proportions of eicosapentaenoic acid (EPA) and palmitic acid in CE and AT moderately correlated with dietary intake, whereas correlations of other FAs were weaker or absent. Proportions of EPA and DHA in CE and AT were positively associated with the total energy-adjusted fish intake. Results were confirmed in adequate reporters as identified by the Goldberg cutoff method. These relationships held constant, regardless of a GFR above or below 45 mL/min per 1.73 m(2) or the prevalence of microalbuminuria. Proportions of EPA, DHA, palmitic and linoleic acid in serum CE and AT are good indicators of their dietary intake in men with CKD. They can be considered valid biomarkers for epidemiological studies and assessment of compliance.

High levels of stearic acid, palmitoleic acid, and dihomo-γ-linolenic acid and low levels of linoleic acid in serum cholesterol ester are associated with high insulin resistance

The association of fatty acid composition with insulin resistance and type 2 diabetes has been reported in Western populations, but there is limited evidence of this association among the Japanese, whose populace consume large amounts of fish. To test the hypothesis that high palmitic, palmitoleic, and dihomo-γ-linolenic acids and low levels of linoleic and n-3 fatty acids are associated with higher insulin resistance among the Japanese, the authors investigated the relationship between serum fatty acid composition and serum C-peptide concentrations in 437 Japanese employees aged 21 to 67 years who participated in a workplace health examination. Serum cholesterol ester and phospholipid fatty acid compositions were measured by gas-liquid chromatography. Desaturase activity was estimated by fatty acid product-to-precursor ratios. A multiple regression was used to assess the association between fatty acid and C-peptide concentrations. C-peptide concentrations were associated inversely with linoleic acid levels in cholesterol ester and phospholipid (P for trend = .01 and .02, respectively) and positively with stearic and palmitoleic acids in cholesterol ester (P for trend =.02 and .006, respectively) and dihomo-γ-linolenic acid in cholesterol ester and phospholipid (P for trend < .0001 for both). C-peptide concentrations were not associated with n-3 polyunsaturated fatty acids. C-peptide concentrations significantly increased as δ-9-desaturase (16:1 n-7/16:0) and δ-6-desaturase (18:3 n-6/18:2 n-6) increased (P for trend = .01 and .03, respectively) and δ-5-desaturase (20:4 n-6/20:3 n-6) decreased (P for trend = .004). In conclusion, a fatty acid pattern with high levels of serum stearic, palmitoleic, or dihomo-γ-linolenic acids; δ-9-desaturase (16:1 n-7/16:0) or δ-6-desaturase (18:3 n-6/18:2 n-6) activities; and low levels of serum linoleic acid or δ-5-desaturase (20:4 n-6/20:3 n-6) activity might be associated with higher insulin resistance in Japanese adults.

Childhood serum cholesterol ester fatty acids are associated with blood pressure 27 y later in the Cardiovascular Risk in Young Finns Study

In adults, dietary fatty acids (FAs) modify blood pressure (BP), but it is not known whether childhood FA quality is associated with adulthood BP. The purpose of the study was to investigate links between childhood serum cholesterol ester fatty acid (CEFA) proportions and adulthood systolic blood pressure (SBP) and diastolic blood pressure (DBP). We examined a cohort of 803 boys and girls (aged 3-18 y at baseline in 1980 and followed for 27 y) by using regression models adjusted for the known risk factors of BP. CEFAs were analyzed as markers of dietary FA intake. In men, serum SFA (B = 2.97, P < 0.001 for SBP; B = 1.48, P = 0.015 for DBP), MUFA (B = 0.61, P = 0.001 for SBP; B = 0.27, P = 0.078 for DBP), and omega-3 (n-3) PUFA (B = 5.50, P < 0.001 for SBP; B = 2.47, P = 0.015 for DBP) proportions, which were derived mainly from animal fats in this population, were positively associated with BP, whereas the omega-6 (n-6) PUFA proportion, which was derived mainly from vegetable oils and margarines, was negatively associated with BP (B = -0.56, P < 0.001 for SBP; B = -0.27, P < 0.018 for DBP). Serum cholesterol ester SFA and PUFA associations were supported by dietary intake data. In women, the associations between CEFA proportions and BP were weaker [for SBP: B = 0.36, P = 0.638 (NS) for SFA; B = 0.44, P = 0.019 for MUFA; B = 1.18, P = 0.376 (NS) for n-3 PUFA; and B = -0.33, P = 0.023 for n-6 PUFA]. Our findings suggest that fat quality as reflected in the serum cholesterol ester fraction in childhood is independently associated with adulthood BP particularly in men but also, to some extent, in women.